Metabolomics Analysis Reveals the Differential Metabolites and Establishes the Therapeutic Effect Prediction Nomogram Among CP/CPPS Patients Who Respond or Do Not Respond to LiST

OBJECTIVE: Low-intensity shockwave therapy (LiST) has been applied in the clinical treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but few studies have focused on the prediction of its therapeutic effect before treatment. METHODS: Seventy-five CP/CPPS patients from our institute between July 2020 and May 2021 were enrolled and received 3 Hz, 0.25 mJ/mm(2) LiST once a week over the course of four weeks. The scores of the NIH-CPSI, IPSS questionnaire and demographic features before treatment were recorded. The plasma before LiST treatment was also collected, while liquid chromatography-tandem mass spectrometry was used to detect the metabolites. Least absolute shrinkage and selection operator (LASSO) regression analysis was employed to identify the prediction metabolites and generate the metabolism score. Receiver operating characteristic curves and calibration curves were drawn to assess the prediction accuracy of the nomogram. RESULTS: Twelve metabolites were identified at incomparable levels before and after LiST treatment. The metabolism score generated by LASSO analysis presented a perfect prediction value (AUC: 0.848, 95% CI: 0.719-0.940) in the training cohort and further increased to 0.892 (95% CI: 0.802-0.983) on the nomogram, which accompanied with the NIH-CPSI scores and age. Similar results of the metabolism score (AUC: 0.732, 95% CI: 0.516-0.889) and total nomogram (AUC: 0.968, 95% CI: 0.909-1.000) were obtained in the testing cohort. Further enrichment of the 12 metabolites indicated that the glycine and serine metabolism pathway was involved in the LiST treatment. CONCLUSION: We used our system to accurately and quantitatively measure plasma metabolites and establish a predictive model to identify suitable patients for LiST treatment.